L33 Breast Pathology Part II - Malignancy onwards

Question 1

What are the genetic changes related to Familial Brest carcinoma (10%) ? (4)

Answer 1

1. BRCA1/2 (tumor suppressor gene)
2. AD inheritance with variable penetrance
3. TP53 germline mutation
4. PTEN mutation (Cowden syndrome/ multiple harmatoma syndrome - Benign overgrowths called hamartomas as well as an increased lifetime risk of breast, thyroid, uterine, and other cancers.)

Question 2

AD inheritance cause of familial breast carcinoma is associated with triple-ve Ca breast, Ca ovary and CA male breast.
What does it meant by triple -ve ?

Potential treatment?

Answer 2

Negativity for ER,PR and HER2

Tx: PARP1 inhibitor

Question 3

Which of the following regarding malignant breast tumors are correct?

A. Family history would cause a 50% increase in risk of malignancy

B. American black females are prone to have a younger onset and higher grade

C. Malignancy is rare before 25 years old and has a steady increase until 65

D. Late menarche is a risk factor

E. Age of having the first child >30 causes an increase risk.

Answer 3

All except D

D: Early menarche and Late menopause = increased estrogen exposure

Question 4

Risks of CA breast related to oestrogen exposure?

other than early menarche, late menopause, age of having 1st child

Answer 4

1. Parity - uninterrupted menstrual cycle (interrupted = abortion, pregnancy, lactation, reduced breast cancer)
2. Obesity in post-menopause: peripheral fat instead of ovary in post-menopause women for oestrogen production
3. Proliferative breast lesion: atypical hyperplasia (4x)
4. Carcinoma of contralateral breast/endometrium

Question 5

What is carcinoma in situ?

Answer 5

Malignant cells not yet penetrate the basement membrane (beneath myoepithelial cells)

Question 6

What are the 2 types of carcinoma in situ of the breast? (2)

Main diference? (2)

Answer 6

1. Ductal carcinoma in situ (DCIS)
2. Lobular carcinoma in situ (LCIS)
   (not staged as CIS but as benign disease in 8th AJCC)
3. DCIS: malignant cells in the ducts without invasion
4. LCIS: malignant cells in the lobules without invasion
   ( loss of E-cadherin: loose)

Question 7

What is Comedo DCIS?

What grade does it belong to?

Answer 7

‘Plug’
Breast duct is completely plugged by cancer cells, rapid proliferation of the cell > centre undergoes necrosis.

= High grade

Question 8

Which of the following regard DCIS and LCIS are incorrect?

A. Both are diagnosed by core biopsy

B. Both are asymptomatic

C. DCIS is palpable while LCIS is not

D. Pleomorphic microcalfications can be seen in mammography of DCIS due to dystrophic calcifications, while no abnormality to LCIS

E. Both can be low grade or high grade

Answer 8

C
- Both impalpable
DCIS: inflammation and fibrosis at the peripheral of cancer > impalpable

LCIS: loose cell arrangement

Question 9

Why would DCIS and LCIS cause CA risk respectively? (2)

How many percent increase/year?

Answer 9

DCIS
- Precursor to invasive ductal carcinoma of the same breast -1%/year

LCIS
- Precursor and marker of bilateral invasive carcinoma (ductal/lobular) -1%/year

Question 10

Treatment for DCIS? (3)

Answer 10

1. Breast-conservation therapy +/- RT
2. Total mastectomy if diffuse breast involvement
3. Adjuvant: Tamoxifen (if ER +ve) ( selective estrogen receptor modulator used to prevent breast cancer)

Question 11

Treatment for LCIS? (3)

Answer 11

1. Lifelong close surveillance
2. High risk patients: Bilateral total masectomy
3. Adjuvant: Tamoxifen if ER+ve

Question 12

Eczematous changes and crusting exudate of the nipple. Dx? (1)

Pathology?(2)

Answer 12

Paget disease of the nipple

• infiltration of nipple epidermis by malignancy cells
• a/w underlying carcinoma (DCIS/invasive ductal carcinoma)

Question 13

Name the 2 types of invasive carcinoma of the breast.

Answer 13

1. Invasive ductal carcinoma NOS (MC: 80%)

(not otherwise specified = no specific histomorphological feature)

2. Invasive lobular carcinoma (<20%)

Question 14

What are the differences in

1) Presentation
2) Molecular markers

between Invasive ducal VS lobular carcinoma?

Answer 14

1) Presentation
- IDC: palpable firm mass
- ILC: Non-palpable firm mass

2) Molecular markers
- IDC: ER, PR, HER2

• ILC: ER/PR+ with HER2 -ve usually

Question 15

Pathology of invasive ductal carcinoma? (3)

Answer 15

1. Desmoplasic reaction (dense fibrotic) = inflammation + fibrosis
2. Hard, retracted apperance
3. Invasive nests

Question 16

Pathology of invasive lobular carcinoma? (3)

Answer 16

1. Loss of E-cadherin: bull’s eye pattern (tumor cells surround ducts and lobules)/

loosely arranged in strands/cords/single cell

(when cells arranged in a line> suspect ILC)

Question 17

Inflammatory and metaplastic histomorphological features in CA breast points to poor prognosis.

How about good prognosis? (4)

Answer 17

• Mucinous
• Tubular
• Secretory
• Adenoid cystic

Question 18

Which of the following are indicators for therapy choice?

A. Histology
B. Molecular markers
C. Both
D. Neither

Answer 18

B only!

A: only for prognosis

Question 19

Histological grading of a breast tumor is by looking at? (3)

Answer 19

1. Nuclear morphology
2. Mitosis
3. Tubule formation

Question 20

How does LN spread in breast tumors?

Answer 20

Axillary >
Internal mammary > Supraclavicular

> Lungs, bone, liver, adrenal

Question 21

What are sentinel lymph nodes?

How is it identified?

Answer 21

First nodes to which cancer cells may spread from a tumor = axilla.

Best: intra-operatively
1. Injection of methylene blue + radioactive isotope (sulphur colloid) around the tumour

2. after 5mins -1hr - 1st excise the 1st draining lymph node (groups)

Question 22

if -ve sentinel lymph nodes, still require axillary dissection?

Answer 22

No, otherwise may case lymphedema of upper limb/ risk of lymphangiosarcoma

Question 23

ER/PR+ve means which 2 types ?

Treatment? (2)

Answer 23

Luminal A: LG
Luminal B: HG

Tx:
1. Tamoxifen - SERM (selective estrogen receptor modulator)

2. Aromatase inhibitors e.g. anastrozole
   (aromatase: testosterone > estrogen)

Question 24

ER/PR -ve > check for?

Relative prognosis?

Answer 24

HER2 +ve: HG

> poor prognosis, Tx: trastuzumab (Herceptin) (monoclonal antibody)

HER2 -ve = triple
negative: HG (worst prognosis)

> Chemotherapy needed

Question 25

Proliferative rate is assessed by?

Answer 25

Ki67
Low = Good Px
High = Poor Px > dose dense chemotherapy

Others:
Chromosome aberration in CA breast prognosis?

Diploid = Good
Aneuploid = Poor (abnormal number of chromosomes)

Question 26

Drugs for

1. Immunotherapy
2. BRCA mutation

Answer 26

1. PD-L1 inhibitor

2. PARP inhibitors

Question 27

Which of the following regarding gene based assays in CA breast is correct?

A. Oncotype Dx: 21 genes for recurrence score for early stage, node -ve, ER+ CA breast

B. Oncotype Dx is predicative for adjuvant chemotherapy

C. Mammaprint is for recurrence of early stage CA breast

D. Prosigna predicts 10 years distant recurrence

E. Calculates recurrence risk and thus therapeutic dose

Answer 27

All of the above

Question 28

Gynaecomastia in male = fibrocystic change-equivalent in female

Reason? (3)

Answer 28

High estrogen state

1. Increase in estrogen
   - digoxin
   - puberty/old age
   - liver failure (stigmata of chronic liver disease)
2. Decrease in androgen
   - leuprolide (Tx for CA prostate)
3. Defect in androgen receptor
   - androgen insensitivity syndrome
   - spironolactone

Question 29

Carcinoma of breast in male

A. 1:100 ratio M:F
B. Presents late
C. Invades early
D. Histology similar to carcinoma in female
E. Extend outside breast even if it is rudimentary (early stage)

Answer 29

All of the above